Patent License Agreement - F. Hoffman-La Roche Ltd., Roche Molecular Systems Inc. and Invitrogen Corp.
PATENT LICENSE AGREEMENT
This is a patent license agreement ("Agreement"), and effective as of July 1,
1998.
by and among
F. Hoffmann-La Roche Ltd, a Swiss corporation with offices at Grenzacherstrasse
124, CH-4070 Basel, Switzerland
and
Roche Molecular Systems, Inc., a Delaware corporation having an office at 1080
U.S. Highway 202, Branchburg Township, Somerville, New Jersey 08876-1760
(BOTH OF WHICH ARE REFERRED TO HEREIN AS "ROCHE"),
and
Invitrogen Corporation, a Delaware corporation with offices at 1600 Faraday
Avenue, Carlsbad, California 92008
(HEREINAFTER REFERRED TO AS "INVITROGEN")
***********************
BACKGROUND
A. ROCHE owns United States Patents Nos. 4,683,195, 4,683,202 and 4,965,188 and
the corresponding foreign counterpart patents and patent applications,
describing and claiming nucleic acid amplification processes including,
INTER ALIA, a process known as the polymerase chain reaction ("PCR")
process.
B. ROCHE also owns certain patents and patent applications, filed worldwide,
relating to purified natural, as well as recombinant, thermostable DNA
polymerases, as well as compositions including said polymerases, including
for example, DNA polymerases isolated from Thermus species and fragments and
mutants thereof.
C. ROCHE also owns United States Patent No. 5,075,216 and the corresponding
foreign counterpart patents and patent applications relating to sequencing
with Taq DNA polymerase.
D. ROCHE also owns United States Patent Nos. 5,407,800, 5,322,770 and 5,310,652
and the corresponding foreign counterpart patents and patent applications
relating, inter alia, to reverse transcription using a thermostable
polymerase.
E. The Perkin-Elmer Corporation ("P-E") has exclusive rights in certain fields,
including the field of research, pursuant to an agreement dated December 11,
1991 with ROCHE and has
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certain rights to grant sublicenses in said fields. Under separate
agreements between ROCHE and P-E and in consideration of a share of
royalties due hereunder, P-E has released ROCHE from so much of P-E's rights
in the aforementioned fields as is necessary for ROCHE to convey to
INVITROGEN the rights specified in this Agreement.
F. INVITROGEN wishes to obtain the right to make, use and sell to the research
and to other markets products covered by AMPLIFICATION PATENT RIGHTS,
POLYMERASE PATENT RIGHTS, RT AND RT-PCR PATENT RIGHTS and/or SEQUENCING
PATENT RIGHTS, as hereinafter defined.
G. In structuring the present Agreement, the Parties have considered the
possibility that novel polymerases may be developed by INVITROGEN (and
others) that are useful in, and that without a license from ROCHE,
INVITROGEN may not pass on to its customers the right to use said
polymerases in the PCR PROCESS, or in process covered by RT or RT-PCR PATENT
RIGHTS. It is INVITROGEN's desire to promote and sell such internally
developed, or licensed or purchased polymerases for use in the PCR PROCESS,
or in processes covered by RT and/or RT-PCR PATENT RIGHTS and to pass on to
the purchaser such a license and ROCHE is willing to permit INVITROGEN to do
so.
H. In addition, the parties take note that INVITROGEN may market the products
licensed hereunder in conjunction with other products, components or
materials, both separately or together, and in various package arrangements,
which may be useful in the PCR PROCESS, and/or processes covered by RT AND
RT-PCR PATENT RIGHTS. Taking this into consideration, for the mutual
convenience of the parties, the products on which INVITROGEN will pay a
royalty, that is the royalty base, will include those products on which
INVITROGEN will pay a royalty, that is the royalty base, will include those
products as specifically described below that are adapted for, promoted or
supported for use with the patent rights licensed herein. Futhermore, in an
effort to minimize customer confusion as to which INVITROGEN products in
fact permit the customer to practice the PCR PROCESS, and/or processes
covered by RT AND RT-PCR PATENT RIGHTS without additional licenses,
INVITROGEN agrees, as is further described below, to give special
consideration to the manner in which it promotes and sells its other
products which may be useful in the PCR PROCESS and/or processes covered by
RT AND RT-PCR PATENT RIGHTS but which are not specifically licensed by ROCHE
for that purpose.
NOW THEREFORE, for and in consideration of the mutual covenants contained
herein, ROCHE and INVITROGEN ("the Parties") agree as follows:
1. DEFINITIONS
For the purpose of this Agreement, and solely for that purpose, the terms set
forth hereinafter shall be defined as follows:
1.1 The term "AFFILIATE" of a designated party to this Agreement shall mean:
a) and organization of which fifty percent (50%) or more of the
voting stock is controlled or owned directly or indirectly by
either party to this Agreement;
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b) an organization which directly or indirectly owns or controls
fifty percent (50%) or more of the voting stock of either party to
this Agreement;
c) an organization, the majority ownership of which is directly or
indirectly common to the majority ownership of either party to
this Agreement; and
d) an organization under a), b), or c) above in which the amount of
said ownership is less than fifty percent (50%) and that amount is
the maximum amount permitted pursuant to the law governing the
ownership of said organization.
It is understood and agreed, however, that the term "AFFILIATE" shall not
include Genentech Inc., a Delaware corporation.
1.2 "AMPLIFICATION PATENT RIGHTS" shall mean the nucleic acid amplification
processes covered by United States Patent Nos. 4,683,195, 4,683,202 and
4,965,188, and those claims in foreign patents and patent applications
which correspond to issued claims in the above patents and which foreign
patents and patent applications claim priority from patent applications
on which the above patents are based, and access to which patents and
patent applications are necessary for INVITROGEN to manufacture, use and
sell products which include a label license under AMPLIFICATION PATENT
RIGHTS, in accordance with the rights granted in Sections 2.2 - 2.3
hereto.
1.3 "APPLICATION FIELDS" shall mean those fields listed in Appendix A.
1.4 "APPLICATIONS KIT" shall mean a LICENSED PRODUCT in combination with all
such other reagents, enzymes or other materials as are necessary to
perform a PCR-based assay or nucleic acid sequencing in the APPLICATION
FIELD for which it is sold.
1.5 "AUTHORIZED THERMAL CYCLER" shall mean a thermal cycler or temperature
cycling instrument whose use in automated performance of the PCR PROCESS
in the RESEARCH FIELD and APPLICATION FIELDS is covered by the up-front
fee component of a PCR PROCESS license. The up-front component of that
license may be purchased from P-E. Alternatively, the up-front component
of that license may be obtained through the purchase of thermal cycler(s)
or temperature cycling instrument(s) bearing a valid label conveying the
up-front PCR PROCESS license component.
1.6 "INVITROGEN ENZYME" shall mean any thermostable polymerase that is not a
ROCHE PATENTED ENZYME, is not within POLYMERASE PATENT RIGHTS, and is
developed by INVITROGEN or is purchased or licensed by INVITROGEN from a
third party, which enzyme may be used in or with the PCR PROCESS and/or
processes covered by RT AND RT-PCR PATENT RIGHTS. An enzyme shall not be
included in this definition if INVITROGEN demonstrates to ROCHE'S
satisfaction that said enzyme is in fact used predominantly for other
than the PCR PROCESS and/or processes covered by RT AND RT-PCR PATENT
RIGHTS. Unless excluded as provided herein, all sales of said INVITROGEN
ENZYMES are assumed to be for use in the PCR Process and/or processes
covered by RT AND RT-PCR PATENT RIGHTS.
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1.7 "LICENSED APPLICATION PRODUCT" shall mean a) an APPLICATIONS KIT for a
LICENSED APPLICATION FIELD or b) reagents, components or other materials
which are sold in connection with the sale of an APPLICATIONS KIT for a
LICENSED APPLICATION FIELD by INVITROGEN and which are adapted for or
promoted or supported for use by customers in PCR TESTING or nucleic acid
sequencing, or RT AND RT-PCR in APPLICATION FIELDS. As used herein, "PCR
testing" shall include all steps in the analysis of a sample for the
presence or absence of amplifiable nucleic acid from preparation of the
sample to detection and/or analysis of any amplified product.
1.8 "LICENSED FIELDS" shall mean the RESEARCH FIELD and those APPLICATION
FIELDS that are elected or added pursuant to Section 5 of this Agreement
("LICENSED APPLICATION FIELDS").
1.9 "LICENSED PRODUCT" shall mean:
a) a ROCHE PATENTED ENZYME or a INVITROGEN ENZYME used or sold in a
country where the use or sale of such ROCHE PATENTED ENZYME or
INVITROGEN ENZYME would infringe at least one VALID CLAIM of a
patent or patent application within AMPLIFICATION PATENT RIGHTS,
SEQUENCING PATENT RIGHTS or RT AND RT-PCR PATENT RIGHTS; and/or
b) a ROCHE PATENTED ENZYME made, used or sold in a country where the
manufacture, use or sale thereof would infringe a VALID CLAIM of a
patent or patent application within POLYMERASE PATENT RIGHTS.
1.10 "LICENSED RESEARCH PRODUCTS" shall mean any product, including but not
limited to kits, which products consist of or contain a LICENSED PRODUCT
and may include all or some of the following components: buffers,
nucleotides, enzymes, or other reagents or materials. Notwithstanding
the foregoing, it is understood and agreed that such LICENSED RESEARCH
PRODUCT shall not contain, without ROCHE's specific approval, which
approval shall be strictly discretionary with ROCHE, nucleic acid
sequences homologous to the nucleic acid sequences of any human
infectious agent or pathogen.
1.11 "NET SALES" shall mean gross invoice amount less
a) discounts allowed and taken, in amounts customary in the trade,
and
b) sales and/or use taxes and/or duties for particular sales.
No allowance or deduction shall be made for commissions or fees
for collection, by whatever name known.
NET SALES shall be calculated on the basis of sales or transfers
to end users by INVITROGEN or an AFFILIATE or distributor. In the
event INVITROGEN is unable to account for sales to third-party end
users by its distributors, the NET SALES shall be calculated as
the sales price to such distributors multiplied by 1.67, which
factor
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represents a 40% margin allowed to the distributor. Sales to a
third party controlling, controlled by, or under common control
with INVITROGEN, or enjoying a special course of dealing with
INVITROGEN, shall be determined by reference to the listed or
published price for the product sold or transferred which would be
applicable in an arm's length transaction, with an unrelated third
party. In Japan, if INVITROGEN does not use a distributor, but
instead, sales are made to end users through a WHOLESALER, and
INVITROGEN is unable to account for sales to third-party end users
by said WHOLESALER in Japan, the Net Sales shall be calculated as
the sale price to such WHOLESALER multiplied by 1.20, which factor
represents a 17% margin allowed to the WHOLESALER in Japan.
INVITROGEN and ROCHE agree that ROCHE may amend this factor in the
event that market conditions change such that the prevailing
margin to WHOLESALERS differs from 17% by 2% or more.
1.12 "PCR PROCESS" shall mean the polymerase chain reaction (PCR)
process, which is one of the amplification processes covered by
AMPLIFICATION PATENT RIGHTS.
1.13 "POLYMERASE PATENT RIGHTS" shall mean
a) TAQ PATENT RIGHTS; and
b) those claims of those United States patents and patent
applications listed in Schedule 1 hereto, and those claims
in non-US patents and patent applications which claim
priority from the patents and patent applications on which
the patents and patent applications in Schedule 1 are
based, and access to which patents and patent applications
are necessary for INVITROGEN to manufacture, use and sell
ROCHE PATENTED ENZYMES, other than A TAQ REAGENT, in
accordance with the rights granted in Section 2.2. hereto.
1.14 "RESEARCH FIELD" shall mean the internal use by an end user of a
product solely in applications of the end user (or in applications
of the end user's customer, if the end user is performing contract
research) in scientific research and development; and by way of
example but not by way of limitation, expressly excludes:
a) reportable results generated from clinical applications in
humans or animals such as the detection or measurement,
treatment, prevention or mitigation of disease or other
health-related condition; the detection of pathogens,
detection of genetic disease or genetic predisposition to
disease; tissue transplantation typing; and parentage
determination;
b) the use of PCR to manufacture any products for sale;
c) the commercial application of Taggants, which shall be
defined herein to be the application of the PCR PROCESS to
identify any synthetic nucleotide sequence which has been
inserted, dispersed or applied into a product, substance or
organism in order to identify such product, substance or
organism or to convey other specific information;
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d) quality assurance and quality control, including without
limitation, conformance with specifications, purity, batch
to batch consistency whether performed internally or for
third parties on a commercial basis; and
e) Forensic and Human Identity Applications (as defined in
Appendix A);
f) Environmental Testing Applications (as defined in Appendix
A);
g) Agricultural Plant Applications (as defined in Appendix A);
h) Animal Identity Testing and Positive Trait Breeding
Applications (as defined in Appendix A);
i) Food Testing Applications (as defined in Appendix A).
1.15 "ROCHE PATENTED ENZYME" shall mean
a) a TAQ REAGENT; or
b) an enzyme the manufacture, use or sale of which would be
covered by at least one VALID CLAIM within paragraph (b) of
POLYMERASE PATENT RIGHTS and which ROCHE has agreed to
include in Schedule 2 hereto. Notwithstanding the
foregoing, the Parties understand and agree that ROCHE
shall not be obligated in any way to include any additional
patent rights to those currently listed in Schedule 1.
1.16 "ROYALTY UNIT" shall mean:
a) for a TAQ REAGENT, the equivalence to a unit of AmpliTaq
-Registered Trademark- DNA polymerase as described in
Appendix B, Section I;
b) for a ROCHE PATENTED ENZYME other than a TAQ REAGENT, and
for an INVITROGEN ENZYME, a unit of enzyme (as unit is
defined in INVITROGEN's product specification) multiplied
by the PCR EFFECTIVENESS RATIO as provided in Appendix B,
Section II.
1.17 "RT" shall mean reverse transcription.
1.18 "RT AND RT-PCR PATENT RIGHTS" shall mean those claims of United
States Patent Nos. 5,407,800, 5,322,770, and 5,310,652 and any
reissues thereof and those claims in foreign patents and patent
applications which correspond to issued claims in the above
patents and which foreign patents and patent applications claim
priority from the patent application(s) on which the '800, '770
and '652 patents are based, and access to which patents and patent
applications are necessary for INVITROGEN to manufacture, use and
sell ROCHE PATENTED ENZYMES and INVITROGEN ENZYMES in accordance
with the rights granted in Section 2.5 hereto.
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1.19 "SEQUENCING PATENT RIGHTS" shall mean the claims of United States Patent
No. 5,075,216 and any reissue thereof and those claims in foreign patents
and patent applications which correspond to issued claims in the above
patent and which foreign patents and patent applications claim priority
from the patent application(s) on which the '216 patent is based, and
access to which patents and patent applications are necessary for
INVITROGEN to manufacture, use and sell products pursuant to section 2.4
hereto.
1.20 "TAQ PATENT RIGHTS" shall mean those claims of United States Patent Nos.
4,889,818 and 5,079,352 and any reissues and continuations thereof, but
not continuations in part of the above patents and patent applications,
and those claims in foreign patents and patent applications claiming
priority from a patent application which is a basis for any of the above
US patents or patent applications, which include within their scope a
polymerase encoded by THERMUS AQUATICUS DNA, but only to the extent that
such claims are necessary for INVITROGEN to manufacture, use and sell a
polymerase encoded by THERMUS AQUATICUS pursuant to Section 2.1 hereto,
except that these rights specifically exclude the "Stoffel Fragment"
(Lawyer, et. al. (1993) PCR Methods and Applications 2: 275-287) and the
"Abramson Mutant" (described in and additionally covered by US Patent No.
5,466,591).
1.21 "TAQ REAGENT" shall mean an enzyme the manufacture, use or sale of which
is covered by at least one VALID CLAIM within TAQ PATENT RIGHTS.
1.22 "TERRITORY" shall mean worldwide.
1.23 "VALID CLAIM" shall mean the claim of a patent or pending patent
application which has not been held invalid or otherwise unenforceable by
a court from which no appeal has or can be taken, or has not otherwise
finally been held unpatentable by the appropriate administrative agency.
1.24 "WHOLESALER" shall mean an agent who takes orders from end-user customers
for INVITROGEN products, purchases said products from INVITROGEN,
delivers the products to said customers and collects payment from the
end-user customers. The WHOLESALER does not perform other functions of a
distributor, such as, by way of example but not by way of exclusion,
marketing activities such as participating in trade shows, creating
product advertising, and presenting technical seminars, or pre- and
post-sale technical support of the products. ROCHE and INVITROGEN agree
that this definition is applicable only to the Japanese market.
2. GRANT TO INVITROGEN
2.1 LICENSES UNDER POLYMERASE PATENT RIGHTS
Upon the terms and subject to the conditions of this Agreement, ROCHE
hereby grants to INVITROGEN and INVITROGEN hereby accepts from ROCHE a
royalty bearing
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nonexclusive license in the TERRITORY, without the right to sublicense
except to its current AFFILIATES as specifically provided in Section 2.6,
as follows:
a) under TAQ PATENT RIGHTS, to manufacture, but not to have
manufactured, to use and to sell, strictly under INVITROGEN's or
its Affiliates' own Trademarks, Tradenames and/or label(s), TAQ
REAGENTS; and
b) under POLYMERASE PATENT RIGHTS, to manufacture, but not to have
manufactured, to use and to sell, strictly under INVITROGEN's or
its Affiliates' own Trademarks, Tradenames and/or label(s), ROCHE
PATENTED ENZYMES other than TAQ REAGENTS.
No rights are granted expressly, by implication or by estoppel under
AMPLIFICATION PATENT RIGHTS, SEQUENCING PATENT RIGHTS, RT- and RT-PCR
PATENT RIGHTS or any other ROCHE patent rights by the grant of this
Section.
2.2 LICENSE IN THE RESEARCH FIELD TO CONVEY A LABEL LICENSE AND TO PROMOTE
FOR USE IN PCR
A license under the AMPLIFICATION PATENT RIGHTS for automated performance
of the PCR PROCESS in the RESEARCH FIELD has an up-front fee component
based on the capacity of thermal cyclers used, and a running-royalty
component for each use of the process. In consideration of INVITROGEN's
payment of the license issuance fee and of royalties on sales of LICENSED
RESEARCH PRODUCTS, ROCHE hereby grants to INVITROGEN and INVITROGEN
accepts from ROCHE, in the TERRITORY, limited, nonexclusive rights,
without the right to sublicense except to its current AFFILIATES as
specifically provided in Section 2.6, as follows:
a) INVITROGEN is hereby authorized to sell, strictly under
INVITROGEN's or it Affiliates' own Trademarks, Tradenames and/or
label(s), LICENSED RESEARCH PRODUCTS with a label conveying to
end-user purchasers the running-royalty component of a license
under the AMPLIFICATION PATENT RIGHTS to use such LICENSED
RESEARCH PRODUCTS in or with the PCR PROCESS strictly for such
purchasers' own internal use in the RESEARCH FIELD in conjunction
with a thermal cycler whose use is covered by the up-front fee
component, either by payment to P-E or as purchased, and
b) INVITROGEN may promote LICENSED RESEARCH PRODUCTS for such use in
or with the PCR PROCESS in the RESEARCH FIELD. The up-front
component of the PCR license for research must be obtained by the
end user in order to have a complete license for the automated
performance of the PCR PROCESS. The up-front component may be
purchased from P-E. Alternatively, it may be obtained through the
purchase of thermal cycler(s) or temperature cycling instrument(s)
bearing a valid label conveying to purchasers the up-front
component of the license, that is, an "AUTHORIZED THERMAL CYCLER."
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INVITROGEN may use LICENSED RESEARCH PRODUCTS, on which it pays royalties
hereunder, in accordance with the terms of the label authorized in part a)
above.
2.3 LICENSE IN APPLICATION FIELDS TO CONVEY A LABEL LICENSE AND TO PROMOTE FOR
PCR
A license under the AMPLIFICATION PATENT RIGHTS for automated performance
of the PCR PROCESS in all or some of the APPLICATION FIELDS includes an
up-front fee component as described in Section 2.2 and a running royalty
component. In further consideration of INVITROGEN's payment of license
issuance fees and royalties on sales of LICENSED APPLICATION PRODUCTS,
ROCHE hereby grants to INVITROGEN and INVITROGEN accepts from ROCHE in the
TERRITORY, limited, nonexclusive rights, without the right to sublicense
except to its current AFFILIATES as specifically provided in Section 2.6 as
follows:
a) INVITROGEN is hereby authorized to sell, strictly under INVITROGEN's
or its Affiliates' own Trademarks, Tradenames and/or label(s),
APPLICATION KITS with a label conveying to end-user purchasers the
running-royalty component of a license under the AMPLIFICATION PATENT
RIGHTS to use such APPLICATION KITS in or with the PCR PROCESS
strictly for such purchasers' own internal use in the LICENSED
APPLICATION FIELDS in conjunction with a thermal cycler whose use is
covered by the up-front fee component, either by payment to P-E or as
purchased; and
b) INVITROGEN may promote LICENSED APPLICATION PRODUCTS for such use in
or with the PCR PROCESS in the LICENSED APPLICATION FIELDS. The
up-front component of the PCR license for APPLICATION FIELDS must be
obtained by the end user in order to have a complete license for the
automated performance of the PCR PROCESS. The up-front component may
be purchased from P-E. Alternatively, it may be obtained through the
purchase of thermal cycler(s) or temperature cycling instrument(s)
bearing a valid label conveying to purchasers the up-front component
of the license, that is, an "AUTHORIZED THERMAL CYCLER."
INVITROGEN may use APPLICATION KITS, on which it pays royalties hereunder,
in accordance with the terms of the label authorized in part a) above.
24. LICENSE IN THE RESEARCH FIELD AND LICENSED APPLICATION FIELDS TO CONVEY A
LABEL LICENSE AND TO PROMOTE FOR USE IN SEQUENCING.
In further consideration of INVITROGEN's payment of license issuance fees
and royalties on sales of LICENSED RESEARCH PRODUCTS and LICENSED
APPLICATION PRODUCTS, ROCHE hereby grants to INVITROGEN and INVITROGEN
accepts from ROCHE in the TERRITORY, limited nonexclusive rights, without
the right to sublicense except to its current AFFILIATES as specifically
provided in Section 2.6, as follows:
a) INVITROGEN is authorized to sell, strictly under INVITROGEN's or its
Affiliates' own Trademarks, Tradenames and/or labels(s)., LICENSED
RESEARCH PRODUCTS in the RESEARCH FIELD and APPLICATIONS KITS in the
LICENSED
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APPLICATION FIELDS with a label conveying to end-user purchasers a
license under the SEQUENCING PATENT RIGHTS to use such LICENSED
RESEARCH PRODUCTS and APPLICATIONS KITS for such purchasers' own
internal use in sequencing without any rights under the AMPLIFICATION
PATENT RIGHTS in the RESEARCH FIELD or the LICENSED APPLICATION FIELDS
for which the APPLICATIONS KITS are sold; and
b) INVITROGEN may promote LICENSED RESEARCH PRODUCTS for use in the
RESEARCH FIELD and APPLICATIONS KITS for use in the LICENSED
APPLICATION FIELDS for which the APPLICATIONS KITS are sold in
processes within the SEQUENCING PATENT RIGHTS.
INVITROGEN may use LICENSED RESEARCH PRODUCTS and APPLICATIONS KITS, on
which it pays royalties hereunder, in accordance with the terms of the
label authorized in part a) above.
25. LICENSE IN THE RESEARCH FIELD AND LICENSED APPLICATION FIELDS TO CONVEY
RIGHTS TO PERFORM AND PROMOTE FOR USE IN RT AND RT-PCR
In further consideration of INVITROGEN's payment of license issuance fees
and royalties on sales of LICENSED RESEARCH PRODUCTS and LICENSED
APPLICATION PRODUCTS, ROCHE hereby grants to INVITROGEN and INVITROGEN
accepts from ROCHE in the TERRITORY, limited nonexclusive rights, without
the right to sublicense except to its current AFFILIATES as specifically
provided in Section 2.6, as follows:
a) INVITROGEN is authorized to sell, strictly under INVITROGEN's or its
Affiliates' own Trademarks, Tradenames and/or labels(s), LICENSED
RESEARCH PRODUCTS in the RESEARCH FIELD and APPLICATIONS KITS in the
LICENSED APPLICATION FIELDS which convey to the end-user purchasers a
license under RT AND RT-PCR PATENT RIGHTS to use such LICENSED
RESEARCH PRODUCTS and APPLICATIONS KITS for such purchasers' own
internal use in reverse transcription and reverse transcription
coupled with PCR amplification; and
b) INVITROGEN may promote LICENSED RESEARCH PRODUCTS for use in the
RESEARCH FIELD and APPLICATIONS KITS for use in the LICENSED
APPLICATION FIELDS in processes within RT AND RT-PCR PATENT RIGHTS.
INVITROGEN may use LICENSED RESEARCH PRODUCTS and APPLICATIONS KITS on
which it pays royalties hereunder, in accordance with the terms defined in
part a) above.
2.6 LIMITED RIGHT TO GRANT SUBLICENSES
a) INVITROGEN expressly acknowledges and agrees that the license pursuant
to this Agreement is personal to INVITROGEN alone, and INVITROGEN
shall have no right to sublicense, assign or otherwise transfer or
share its right, under this license. Notwithstanding the foregoing,
ROCHE hereby grants to INVITROGEN the right to sublicense current
INVITROGEN AFFILIATES, that is AFFILIATES of INVITROGEN
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on the Effective Date of this Agreement. INVITROGEN hereby
accepts that right, and grants to all of its current
AFFILIATES, and on their behalf accepts, sublicenses as
provided herein. INVITROGEN's AFFILIATES shall not have the
right to grant further sublicenses to any other AFFILIATE or
third party.
b) INVITROGEN shall provide prior written notice to ROCHE of
AFFILIATES operating under its sublicense. Sublicenses to
AFFILIATES of INVITROGEN shall accord with all requirements of
this Agreement and shall include the following terms and
conditions:
i) That the sublicense is co-terminus with this Agreement
as to term and TERRITORY, except as provided below;
ii) To provide INVITROGEN with such complete and accurate
information as is necessary to calculate the NET SALES
of each sublicensed product sold or otherwise
transferred by such AFFILIATE;
iii) To grant to ROCHE the right to inspect under the terms
and conditions in Section 4.4; and
iv) To be bound by all terms and conditions of this
Agreement, including without limitation, the indemnity
provisions of Section 11.
Notwithstanding the foregoing, INVITROGEN shall remain
primarily responsible both for its and its sublicensed
AFFILIATES' performance under this Agreement.
c) Unless terminated sooner pursuant to Section 6 herein, any
sublicense to an AFFILIATE shall terminate immediately without
any notice or action on the part of INVITROGEN if:
i) Such sublicense no longer meets the definition of an
AFFILIATE set forth in Section 1.1 hereof; or
ii) INVITROGEN sells its business in LICENSED PRODUCTS to
another person.
In the event of termination on either of the bases set forth in
Section 2.6 c i) or ii) above, then all rights granted to and
obligations undertaken by the sublicensee and INVITROGEN under
such sublicense shall terminate immediately without any action
on the part of INVITROGEN, the AFFILIATE or ROCHE, except for
the rights and obligations surviving termination set forth in
Sections 6.7 and 6.8 herein, and INVITROGEN shall provide
written notice to ROCHE of such termination.
d) No sublicensed AFFILIATE shall have the right to assign or
otherwise transfer its sublicense in whole or in part to any
other AFFILIATE or third party, whether by written instrument
or by operation of law. An assignment of a sublicense in
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<PAGE>
violation of the foregoing sentence shall include, but is not
limited to, either of the following occurrences:
i) The sale, directly or indirectly, to any third party of
a beneficial interest in fifty percent (50%) or more of
the outstanding voting securities of such AFFILIATE; or
ii) The issuance or sale to any third party of a class of
securities of INVITROGEN, the interest dividend or other
distribution on which is measured in substantial part by
the performance of such AFFILIATE such that such third
party, acting alone or in concert with other third
parties, become the beneficial owner of fifty percent
(50%) or more of such class of INVITROGEN securities.
e) Nothing herein shall prohibit INVITROGEN from distributing
LICENSED PRODUCTS on behalf of any sublicensed AFFILIATE.
2.7 Except as is specifically provided herein, this Agreement shall not
limit the rights of ROCHE in any way. It is specifically understood
that as between the Parties to this Agreement, ROCHE reserves the
right itself or through its AFFILIATES to practice under POLYMERASE
PATENT RIGHTS, SEQUENCING PATENT RIGHTS, RT AND RT-PCR PATENT RIGHTS
and AMPLIFICATION PATENT RIGHTS, including the PCR PROCESS itself, and
to sublicense, assign or otherwise transfer such rights to others for
any purpose whatsoever.
2.8 INVITROGEN shall affix to each particular LICENSED RESEARCH PRODUCT or
LICENSED APPLICATIONS PRODUCT licensed hereunder, either on a product
insert accompanying the product or on the product itself, one of the
labels described in Appendix C, as ROCHE shall direct, or such other
label as ROCHE may direct from time to time. Such changes in labeling
shall be subject to the approval of INVITROGEN, which shall not be
unreasonably withheld. As to the labels set forth in Appendix C,
INVITROGEN understands and agrees that the notices numbered 1 through
5 reflect ROCHE's present label licensing policy and shall be used on
the labels for INVITROGEN products as appropriate. In regard to any
changes in labels directed by ROCHE, INVITROGEN shall have a
reasonable time period over which to change its labels.
2.9 a) INVITROGEN hereby covenants that it shall sell, market and
otherwise promote products licensed hereunder in accordance
with the terms of this Agreement and it shall use its best
efforts, as described herein, and shall contractually require
all of its distributors to also use their best efforts, as
described herein, to ensure that these products are sold in
compliance with the letter and intent of this Agreement. To
that end, INVITROGEN and its distributors shall prominently
display in catalogues and brochures describing LICENSED
RESEARCH PRODUCTS and/or LICENSED APPLICATION PRODUCTS, the
label license statements as described in Section 2.8 and
Appendix C. Furthermore, in advertisements or any other
materials intended for distribution to third parties and
referring in any way to
Enzyme/PCR Research Products 12 v.2061097
<PAGE>
products licensed hereunder and the use of said products in the PCR PROCESS,
but in which it is not practical to include the complete label license
statements, INVITROGEN will include a comparable restriction on use as
follows:
"Purchase of this product [or product name] is accompanied by a limited
license to use it in the Polymerase Chain Reaction (PCR) process
[and RT or other as appropriate] for ["field"] in conjunction with a thermal
cycler whose use in the automated performance of the PCR process is covered
by the up-front license fee, either by payment to Perkin-Elmer or as
purchased, i.e., an authorized thermal cycler."
or other statement approved in writing by ROCHE.
b) INVITROGEN agrees that once it is notified by ROCHE or once it
independently becomes aware that a particular purchaser is using or
intends to use any product licensed herein in violation of AMPLIFICATION
PATENT RIGHTS, SEQUENCING PATENT RIGHTS, or RT AND RT-PCR PATENT RIGHTS,
INVITROGEN shall immediately notify said purchaser in writing that such
use is unlicensed and that a license for said use must be obtained from
ROCHE or P-E. INVITROGEN shall also require sublicensed AFFILIATES and
distributors to report to INVITROGEN any unlicensed activities of which
they become aware. INVITROGEN further agrees that continued or resumed
sales by INVITROGEN, a sublicensed AFFILIATE or a distributor, to a
particular purchaser of which INVITROGEN was previously notified or is
otherwise aware is distributing/using any licensed product in violation of
AMPLIFICATION PATENT RIGHTS, RT AND RT-PCR PATENT RIGHTS or SEQUENCING
PATENT RIGHTS, shall constitute a breach of this Agreement under Section 6.5
of the Agreement. A written certification by a distributor or purchaser which
is executed by an officer of said distributor or purchaser which officer may
legally bind the company, that it has ceased infringing the AMPLIFICATION
PATENT RIGHTS, RT AND RT-PCR PATENT RIGHTS and/or SEQUENCING PATENT RIGHTS
or, alternatively, that it does not infringe said patent rights, or a
written certification by INVITROGEN which is executed by an officer of
INVITROGEN which officer may legally bind INVITROGEN that sales to such
distributor or purchaser have ceased, shall be a cure under Section 6.5.
c) Pursuant to the foregoing general requirements, INVITROGEN shall, when it
receives an order for a LICENSED RESEARCH PRODUCT from any customer, which
INVITROGEN recognizes as significantly exceeding that customer's typical
usage requirements, contact the customer and specifically inform the
customer that the AMPLIFICATION PATENT RIGHTS, RT AND RT-PCR PATENT RIGHTS
and/or SEQUENCING PATENT RIGHTS conveyed to customer with the sale of such
LICENSED RESEARCH PRODUCT are limited for use by the customer for internal
research only and that no other rights under the AMPLIFICATION PATENT RIGHTS,
RT AND RT-PCR PATENT RIGHTS and/or SEQUENCING PATENT RIGHTS outside the
LICENSED FIELD are conveyed. Said customers shall be required to furnish a
written certification that customer intends to use said LICENSED RESEARCH
PRODUCT without violating the
Enzyme/PCR Research Products 13 v.2061097
<PAGE>
AMPLIFICATION PATENT RIGHTS, RT AND RT-PCR PATENT RIGHTS or the SEQUENCING
PATENT RIGHTS.
d) INVITROGEN agrees that it shall provide to ROCHE a copy of each of its
notices to purchasers/distributors (as well as a copy of each
purchaser/distributor's certification of compliance) pursuant to this
Section 2.9.
e) The Parties understand and hereby agree that INVITROGEN shall have no
obligation to monitor or police its customers' payment of the up-front fee
component of a PCR license for research or the thermal cycler
"authorization" fee described in Section 1.5. INVITROGEN's obligations
hereinunder in regard to AUTHORIZED THERMAL CYCLERS shall be limited to
providing the label license as specified in Section 2.8 and Appendix C.
However, INVITROGEN agrees not to knowingly promote, directly or through
its distributors, the unlicensed use of PCR with the ROCHE PATENTED
ENZYMES or INVITROGEN ENZYMES in the RESEARCH FIELD or APPLICATION FIELDS
in thermal cyclers for which the up-front license fee has not been paid
(not authorized).
INVITROGEN and ROCHE agree that ROCHE will enforce its rights and will use
its best efforts to cause P-E to enforce its rights with regard to
customers of INVITROGEN using thermal cyclers that are not "authorized" in
the same manner ROCHE and P-E treat their own customers in the same
circumstances.
2.10 Roche hereby grants to INVITROGEN the right and INVITROGEN accepts and
agrees to credit ROCHE as the source of patent rights in INVITROGEN's
promotional materials, including for example advertisements, product
inserts and data sheets, intended for distribution to third parties as
follows:
"This product is sold under licensing arrangements with F. Hoffmann-La
Roche Ltd, Roche Molecular Systems, Inc. and The Perkin-Elmer
Corporation."
Such reference will be reasonably prominent and in materials (for example
catalogues) containing multiple product descriptions, will be directly
associated with information on each specific product covered by this
Agreement.
2.11 In accordance with Section 2.6 b iv), sublicenses granted by INVITROGEN
shall specifically require the sublicensee to comply with INVITROGEN's
obligations under Sections 2.7-2.10.
3. GRANT TO ROCHE
3.1 If INVITROGEN elects to market a INVITROGEN ENZYME or elects to license
third parties to make, use or sell a INVITROGEN ENZYME, ROCHE shall have
an option to negotiate a nonexclusive license to manufacture and sell
directly or through distributors such INVITROGEN ENZYME. INVITROGEN shall
notify ROCHE of its election to market or to license third parties to
market INVITROGEN Enzymes within thirty (30)
Enzyme/PCR Research Products 14 v.2061097
<PAGE>
days of INVITROGEN making such an election. ROCHE may exercise the
said option within three (3) years after the receipt of INVITROGEN's
notice. The terms of said licenses shall be negotiated in good faith
by the parties, taking into consideration the relevant market factors
typically considered in such agreements, but any negotiated royalty
shall not exceed 10% of the Net Selling Price of ROCHE to its
customers or distributors. The duration of said license shall be
commensurate with the term of the last to expire of any patent
covering ROCHE's customers' use of such enzyme without further payment
of any kind from end user customers to INVITROGEN or its licensor, if
there is one. If ROCHE does not exercise the option hereunder, ROCHE
shall nonetheless be entitled to a license to make, use or sell said
INVITROGEN ENZYME under the same terms and conditions as the most
favorable nonexclusive license granted by INVITROGEN.
3.2 Sublicenses granted by INVITROGEN are conditioned on the sublicensee's
making a grant equivalent to Section 3.1 to ROCHE.
4. ROYALTIES, RECORDS AND REPORTS
4.1 LICENSE ISSUANCE FEE
For the rights and privileges granted hereunder, INVITROGEN will pay to
P-E a nonrefundable, noncreditable License Issuance fee of *
upon execution of the Agreement.
4.2 ROYALTIES
For the rights and privileges granted under this Agreement, INVITROGEN
shall pay royalties on products licensed hereunder used by INVITROGEN or
its sublicensed AFFILIATES of sold, distributed, or otherwise transferred
by INVITROGEN or its sublicensed AFFILIATES (with or without payment), as
follows below, except as otherwise specifically modified by Section 5.2
and Appendix A:
a) for a ROCHE PATENTED ENZYME or an INVITROGEN ENZYME, per
Royalty Unit for each such enzyme;
b) for LICENSED RESEARCH PRODUCTS and LICENSED APPLICATION PRODUCTS
that include ROCHE PATENTED ENZYMES and/or INVITROGEN ENZYME, *
of the Net Sales of each licensed Research Product and licensed
Application Product or per Royalty Unit for each enzyme
included in such Product, whichever is larger.
c) for LICENSED RESEARCH PRODUCTS which contain neither ROCHE
PATENTED ENZYMES nor INVITROGEN ENZYMES *
Furthermore, the Parties further understand and agree that the royalty
rates provided in subsections a) though c) above shall apply only for
so long as Amplification Patent shall be in force.
* "CONFIDENTIAL PORTION HAS BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION."
Enzyme/PCR Research Products 15 v.2061097
<PAGE>
4.3 Royalties for sales prior to the signature of the Agreement as from the
first commercial sale of products licensed hereunder shall be reported
together with the first report due hereunder in accordance with Section
4.5.
4.4 INVITROGEN shall keep full, true and accurate books of account containing
all particulars which may be necessary for the purpose of showing the
amount payable by way of royalty or by way of any other provision under
this Agreement for itself and its sublicensed AFFILIATES. Such books and
the supporting data shall be open at all reasonable times, for three (3)
years following the end of the calendar year to which they pertain (and
access shall not be denied thereafter, if reasonably available), to the
inspection of an independent certified public accountant retained by
ROCHE for the purpose of verifying INVITROGEN's royalty statements or
INVITROGEN's compliance in other respects with this Agreement. If in
dispute, such records shall be kept until the dispute is settled. The
inspection of records shall be at ROCHE's sole cost unless the inspector
concludes that royalties reported by INVITROGEN for the period being
audited are understated by five percent (5%) or more from actual
royalties, in which case the costs and expenses of such inspection
shall be paid by INVITROGEN.
4.5 INVITROGEN shall within thirty (30) days after the first day of January,
April, July and October of each year deliver to the addresses provided
below a true and accurate royalty report. This report shall be in
accordance with the royalty report form attached hereto as Appendix D.
This report shall be on U.S./ex-U.S. basis and shall give such
particulars of the business conducted by INVITROGEN in the United States
and in territories other than the United States during the preceding
three (3) calendar months as are pertinent to an accounting for royalty
under this Agreement and shall include at least the following:
a) separately itemized quantities of products licensed hereunder that
are used, sold or otherwise transferred by INVITROGEN during those
three (3) months;
b) the ROYALTY UNITS of ROCHE PATENTED ENZYME(S) AND/OR INVITROGEN
ENZYME(S) in each product licensed hereunder and, for each
product, the calculation of ROYALTY UNITS if different from
"activity units" for said enzyme as advertised, marketed or sold
by INVITROGEN;
c) the NET SALES of each LICENSED RESEARCH PRODUCT and LICENSED
APPLICATION PRODUCT;
d) the calculation of net royalties based on a royalty rate as
defined in Section 4.2;
e) the net royalties due. If no royalties are due, it shall be so
reported.
* "CONFIDENTIAL PORTION HAS BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION."
Enzyme/PCR Research Products 16 v.2061097
<PAGE>
The correctness and completeness of each such report shall be attested to
in writing by the responsible financial officer of INVITROGEN's
organization or by INVITROGEN's external auditor or by the chairman or
other head of INVITROGEN's internal audit committee. With respect to
royalties due from sublicenses, attestation by INVITROGEN may be that it
has obtained from sublicensed AFFILIATES attestations complying with the
preceding sentence.
Simultaneously with the delivery of each such royalty report, INVITROGEN
shall pay to P-E the royalty and any other payments due under this
Agreement for the period covered by such report. All amounts payable
hereunder by INVITROGEN shall be payable in United States currency and
sent by the due date, together with the royalty report, to the following
address:
Applied Biosystems Division
The Perkin-Elmer Corporation
850 Lincoln Centre Drive
Foster City, California 94404, U.S.A.
Attn: Licensing Manager
or to such other address as P-E may designate. A copy of the royalty
report shall also be sent to:
Roche Molecular Systems, Inc.
1145 Atlantic Avenue, Suite 100
Alameda, California 94501, U.S.A.
Attn: Licensing Manager
or to such other address as ROCHE may designate.
4.6 Royalties accruing on account of sales in countries other than the United
States shall be payable in United States dollars in amounts based on the
New York rate of exchange as quoted in The Wall Street Journal (WSJ) for
the last business day of each quarter. If the WSJ does not publish any
such rate, a comparable publication shall be agreed upon from time to
time by the parties, and with respect to each country for which such rate
is not published in the WSJ or in a comparable publication, the parties
shall use the applicable rate for such date by the appropriate
governmental agency in such country.
4.7 a) The Parties agree that the royalty rates and unit fees set
forth in Section 4.2 are reasonable in view of the proprietary
rights associated with the products licensed hereunder and the
consequent relative importance of these products in the
marketplace. The Parties also recognize, however, that a
substantive change might occur in the marketplace, including,
for example, a change in ROCHE's proprietary position, or in
the status of technological alternatives that are non-proprietary
to ROCHE, which change in the marketplace might significantly
detract from the value added of the products licensed hereunder
and thereby in light of the royalty schedule of Section 4.2,
potentially makes INVITROGEN's marketing position correspondingly
less competitive. Should such changes occur in the marketplace,
the parties agree to discuss whether adjustments to the financial
terms herein would be appropriate and otherwise acceptable to
ROCHE.
* "CONFIDENTIAL PORTION HAS BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION."
Enzyme/PCR Research Products 17 v.2061097
<PAGE>
b) In an effort to assist INVITROGEN in remaining competitive in
light of such changes in the marketplace, the parties have
specifically agreed that the following mechanism shall be
available to provide INVITROGEN royalty relief if ROCHE
ascertains that P-E's worldwide combined "Average Transaction
Price" ("ATP") for * in a * period (as is provided below)
is less than * per unit, then INVITROGEN'S unit royalty for *
for that same * period shall be * per unit multiplied by the
fraction * [* per unit], but in no event shall INVITROGEN'S
unit royalty be reduced below * per unit for * nor raised
above * per unit. Such ATP calculations shall be made by ROCHE
for the * period preceding * and INVITROGEN shall be
notified * after the beginning of each such * period if it
is or is not entitled to a credit for the * periods
comprising such * period. By way of example as to how said
royalty adjustments will operate, on each *, ROCHE shall
ascertain P-E's ATP for the * period beginning * prior to
said * date and shall calculate the per-unit royalty as above
described. If that per unit royalty is other than * per unit,
ROCHE shall so notify INVITROGEN no later than on *,
respectively, of * so that INVITROGEN may take the
appropriate credit against the royalties next owed.
As used herein, "Average Transaction Price" shall mean the
average transfer price per unit for all * transferred by P-E or
its Affiliates to end users (which, in P-E's case shall mean to
other than ROCHE or ROCHE's Affiliates). "Average Transaction
Price" shall be calculated by dividing the worldwide aggregate
Net Sales of all products transferred by P-E that contain only
* by the worldwide aggregate Units of * contained in those
products. ROCHE represents that it has the right and is able to
obtain access to such information about P-E's Average
Transaction Price (ATP) as is necessary for ROCHE to make the
above (ATP) calculations accurately.
Except as is specifically provided by the mechanism to provide royalty
relief described in Section (b) above, ROCHE shall be under no
obligation to change or renegotiate any sections, provisions or terms
of this Agreement.
4.8 Withholding tax, if any, levied on any royalty and/or on any other
payments to be paid hereunder, will be paid by INVITROGEN to the proper
taxing authority and proof of payment will be sent to P-E. Any such
withholding tax paid by INVITROGEN, will be fully credited against the
royalty due to P-E.
* "CONFIDENTIAL PORTION HAS BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION."
Enzyme/PCR Research Products 18 v.2061097
<PAGE>
4.9 Any amount not being paid by INVITROGEN when due will bear interest
of one and a half percent (1.5%) per month from the due date until
paid.
5. LICENSE IN ADDITIONAL FIELDS
5.1 INVITROGEN may elect at the time of execution of this Agreement, or
shall maintain an option, exercisable for five years from the
signature date of this Agreement, to add APPLICATION FIELDS to the
LICENSED FIELDS.
5.2 Appendix A specifies for each field to which this election and option
applies a license issuance fee, where applicable, and the applicable
royalty rate if such rate is different from that specified in Section
4.2, for each such field. Roche shall have the right to change said
license issuance fees and royalty rate after two years from the
signature of this Agreement for any field which has not become a
LICENSED FIELD pursuant to Section 5.3.
5.3 Each individual field in addition to RESEARCH FIELD will become a
LICENSED FIELD when the respective election and option has been
exercised and the specified license issuance fee for that field has
been paid.
6. TERM AND TERMINATION
6.1 This license is granted retroactively to INVITROGEN as from the date
of first commercial sale of LICENSED PRODUCTS, LICENSED RESEARCH
PRODUCTS and/or LICENSED APPLICATION PRODUCTS and will expire on the
expiration of the last to expire of the patents within AMPLIFICATION
PATENT RIGHTS, SEQUENCING PATENT RIGHTS, POLYMERASE PATENT RIGHTS, RT
AND RT-PCR PATENT RIGHTS to the extent a license of rights under any
of the foregoing surviving Patent Rights is being exercised pursuant
to Sections 2.1 - 2.5 hereto.
6.2 Notwithstanding any other Section of this Agreement, INVITROGEN may
terminate this Agreement for any reason on ninety (90) days' written
notice to ROCHE. If INVITROGEN elects to terminate this Agreement
pursuant to this section, it shall within thirty (30) days of said
notice to ROCHE, also notify each of its customers that INVITROGEN is
no longer licensed under AMPLIFICATION PATENT RIGHTS, POLYMERASE
PATENT RIGHTS, SEQUENCING PATENT RIGHTS or RT AND RT-PCR PATENT RIGHTS.
6.3 Notwithstanding any other section of this Agreement, ROCHE may
terminate this Agreement, effective immediately upon notice of
termination to INVITROGEN, in the event that a third party which is
licensed by ROCHE to manufacture products for use in PCR-based human
diagnostic testing acquires any interest, including but not limited to
an ownership interest, directly or indirectly, in INVITROGEN of 50% or
more.
6.4 The license granted hereunder to INVITROGEN and all sublicenses
granted by INVITROGEN to its AFFILIATES shall automatically terminate
upon i) an adjudication of INVITROGEN as bankrupt or insolvent, or
INVITROGEN's admission in writing of its
Enzyme/PCR Research Products 19 v.2061097
<PAGE>
inability to pay its obligations as they mature; or ii) an assignment
by INVITROGEN for the benefit of creditors; or iii) INVITROGEN's
applying for or consenting to the appointment of a receiver, trustee
or similar officer for any substantial part of its property or such
receiver, trustee or similar officer's appointment without the
application or consent of INVITROGEN, if such appointment shall
continue undischarged for a period of ninety (90) days; or iv)
INVITROGEN's instituting (by petition, application, answer, consent or
otherwise) any bankruptcy, insolvency arrangement, or similar
proceeding relating to INVITROGEN under the laws of any jurisdiction;
or v) the institution of any such proceeding (by petition, application
or otherwise) against INVITROGEN, if such proceeding shall remain
undismissed for a period of ninety (90) days or the issuance or levy
of any judgment, writ, warrant of attachment or execution or similar
process against a substantial part of the property of INVITROGEN, if
such judgment, writ, or similar process shall not be released, vacated
or fully bonded within ninety (90) days after its issue or levy.
6.5 Upon any breach or default of a material term under this Agreement by
INVITROGEN or an AFFILIATE sublicensed by INVITROGEN, this Agreement
may be terminated upon ninety (90) days, written notice to INVITROGEN.
Said notice shall become effective at the end of the ninety-day
period, unless during said period INVITROGEN fully cures such breach
or default and notifies ROCHE of such cure. Such 90-day cure period
shall not apply to any uncontested royalty payments due, which
uncontested payments must be made in accordance with the terms of this
Agreement.
6.6 Upon termination of this Agreement as provided herein, INVITROGEN
shall immediately stop selling products licensed hereunder and all
rights and licenses granted to INVITROGEN by ROCHE hereunder and all
sublicenses granted by INVITROGEN shall automatically revert to or be
retained by ROCHE.
6.7 INVITROGEN's obligations to report to ROCHE and to pay royalties as to
the sale of products licensed and sublicensed hereunder pursuant to
the Agreement prior to termination or expiration of the Agreement
shall survive such termination or expiration.
6.8 Upon termination of this Agreement for any reason, INVITROGEN shall
destroy its inventory of all products licensed hereunder and confirm
such destruction in writing within ten days of the termination of the
Agreement.
7. ENFORCEMENT OF PATENTS
7.1 INVITROGEN shall advise ROCHE promptly, and shall furnish documentary
proof which is reasonably acceptable to ROCHE, upon its becoming aware
of substantial infringement by a third party or parties of an
enforceable patent right (1) within POLYMERASE PATENT RIGHTS by the
sale of "Significant Quantities" of unlicensed stand-alone enzymes in
any country in the TERRITORY, or (2) within AMPLIFICATION PATENT
RIGHTS by the sale of "Significant Quantities" of enzymes not within
POLYMERASE PATENT RIGHTS but which enzymes are actively promoted by
said third party or parties or their AFFILIATES or distributors for
use in AMPLIFICATION PATENT RIGHTS in any country in
Enzyme/PCR Research Products 20 v.2061097
<PAGE>
the TERRITORY. Upon receipt of said written information, ROCHE agrees it
shall, within its reasonable business judgment, take such action as is
required to restrain such infringement.
ROCHE shall be in full compliance with its obligations under this Section
7.1 if, within six (6) months of ROCHE having received said written
information from INVITROGEN about any one infringing party in a
particular country, (1) ROCHE notifies each third party identified by
such acceptable documentary proof of ROCHE's enforceable proprietary
position in the country where infringement is occurring and receives from
such third parties written assurances, which shall be executed by an
officer of each said third party capable of legally binding that party,
that it is not infringing ROCHE's rights, or (2) said infringement has
stopped, or (3) ROCHE has entered into good faith license negotiations
with such third parties, or (4) ROCHE has instituted or is prosecuting an
action for patent infringement against at least one infringing third
party seller which is active in said country. The above six-month period
may be extended with the consent of INVITROGEN.
It is agreed and understood that nothing in this Section 7.1 or this
Agreement shall require ROCHE to sue more than one party at a time or to
sue in more than one country at any one time.
For the purposes of the foregoing clauses, "Significant Quantities" of
unlicensed stand-alone enzymes shall mean (1) in the case of a single
third-party infringer in a particular country, at least 20%, or (2) in
the case of more than one third party seller in a particular country, at
least 40%, of total ROYALTY UNIT turnover, respectively, of all
stand-alone enzyme(s) within POLYMERASE PATENT RIGHTS or thermostable
enzymes not within POLYMERASE PATENT RIGHTS but which are "Actively
Promoted" for use in AMPLIFICATION PATENT RIGHTS, in each country. For
purposes of this Section 7.1, both Parties must agree as to the accuracy
of said 20% or 40% figures before ROCHE is obligated under this Section
7.1 to pursue any remedial course of action vis a vis any third party
with respect to sales of unlicensed stand-alone enzymes. Also, for
purposes of this particular paragraph, "Actively Promoted" shall mean
advertised or technically supported for use in AMPLIFICATION PATENT
RIGHTS.
If ROCHE is provided with the documentary proof of ongoing infringing
sales as above described and ROCHE does not within the six-month period
pursue one of the above options, INVITROGEN shall have the right at the
expiration of the six-month period, or such other period as the parties
have agreed, to reduce its royalty rate for royalties owed on stand-alone
ROCHE PATENTED ENZYMES and/or stand-alone INVITROGEN ENZYMES in said
country by 20%. It is understood and agreed that any royalty reduction
afforded INVITROGEN pursuant to this Section 7 applies only to sold as
stand-alone enzymes and not to kits containing said enzymes.
INVITROGEN's right to reduce its royalties shall terminate and INVITROGEN
shall resume paying full royalties in each country, as of the time (1)
all such parties in such country have either delivered the written
assurances described above or engaged in good
Enzyme/PCR Research Products 21 v.2061097
<PAGE>
faith license negotiations with ROCHE, provided that if said negotiations
do not conclude within one year, INVITROGEN may again abate its royalty
by 20% in the manner described above until the conclusion of a license
with said third party, or (2) the filing or prosecution of an
infringement suit against at least one such party in said country, or (3)
as a result of the written assurances received in accordance with the
foregoing or the conclusion of any licenses or litigations or otherwise,
infringement in fact ceases or is reduced to below "Significant
Quantities".
Notwithstanding the provisions of this Section 7.1, ROCHE and INVITROGEN
understand and specifically agree that nothing in this Section shall
reduce INVITROGEN's royalty for stand-alone enzymes * per Royalty
Unit.
7.2 Section 7.1 shall apply to sublicensed AFFILIATES and to INVITROGEN's
royalty obligations for sales of sublicensed AFFILIATES as if the
sublicensed AFFILIATES were INVITROGEN.
8. CONFIDENTIALITY-PUBLICITY
8.1 To the extent that, in literature for distribution to third parties,
INVITROGEN refers to ROCHE, P-E or the terms of this Agreement, solely by
specific inclusion of the clause provided in Section 2.10, ROCHE hereby
approves of such usage and no further ROCHE review or approval shall be
required for distribution of said literature. If INVITROGEN varies from
the agreed-to clause in Section 2.10, then INVITROGEN agrees to obtain
ROCHE's written approval prior to distributing any written information
including said modified reference to ROCHE, P-E or the terms of this
Agreement. ROCHE's approval shall not be unreasonably withheld or
delayed and, in any event, its decision shall be rendered within three
(3) weeks of receipt of the written information. Once approved, such
materials, or abstracts of such materials, which do not materially alter
the context of the material originally approved may be reprinted during
the term of the Agreement without further approval by ROCHE unless ROCHE
has notified INVITROGEN in writing of its decision to withdraw permission
for such use. Sublicenses are conditioned on the sublicensed AFFILIATES'
specific agreement to be bound by INVITROGEN's obligations under this
Section.
8.2 Each party agrees that any financial, legal or business information or
any technical information disclosed to it (the "Receiving Party") by the
other (the "Disclosing Party") and identified in writing as confidential
in connection with this Agreement shall be considered confidential and
proprietary and the Receiving Party shall not disclose same to any third
party and shall hold it in confidence for a period of five (5) years
following termination of this Agreement and will not use it other than as
permitted under this Agreement provided, however, that any information,
know-how or data which is orally disclosed to the Receiving Party shall
not be considered confidential and proprietary unless such oral
disclosure is reduced to writing and marked confidential and given to the
Receiving Party in written form within thirty (30) days after oral
disclosure thereof. Such confidential and proprietary information shall
include, without limitation, marketing and sales information,
commercialization plans and strategies, research and
* "CONFIDENTIAL PORTION HAS BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION."
Enzyme/PCR Research Products 22 v.2061097
<PAGE>
development work plans, and technical information such as patent
applications, inventions, trade secrets, systems, methods,
apparatus, designs, tangible material, organisms and products and
derivatives thereof. Notwithstanding the above, ROCHE shall have
the right to share royalty reports with P-E.
8.3 The above obligations of confidentiality shall not be applicable
to the extent that:
a) such information is general public knowledge or, after
disclosure hereunder, becomes general or public knowledge
through no fault of the Receiving Party; or
b) such information can be shown by the Receiving Party by its
written records to have been in its possession prior to
receipt thereof hereunder; or
c) such information is received by the Receiving Party from
any third party for use or disclosure by the Receiving
Party without any obligation to the Disclosing Party
provided, however, that information received by the
Receiving Party from any third party funded by the
Disclosing Party (e.g. consultants, subcontractors, etc.)
shall not be released from confidentiality under this
exception; or
d) the disclosure of such information is required or desirable
to comply with or fulfill governmental requirements,
submissions to governmental bodies, or the securing of
regulatory approvals.
8.4 Each party shall, to the extent reasonably practicable, maintain
the confidentiality of the provisions of this Agreement and shall
refrain from making any public announcement or disclosure of this
Agreement or its terms without the prior consent of the other
party, which consent shall not be unreasonably withheld, except to
the extent a party concludes in good faith that such disclosure is
required under applicable law or regulations, in which case the
other party shall be notified in advance.
9. ASSIGNMENT/TRANSFERABILITY
9.1 The rights and licenses granted by ROCHE to INVITROGEN in this
Agreement are personal to INVITROGEN and may not be assigned or
otherwise transferred, including without limitation any purported
assignment or transfer that would arise from a sale or transfer of
INVITROGEN's business (or any portion of said business). Any
attempted assignment or transfer shall be void and shall
automatically terminate all rights of INVITROGEN under this
Agreement.
9.2 ROCHE may assign all or any part of its rights and obligations
under this Agreement at any time without the consent of
INVITROGEN. INVITROGEN agrees to execute such further
acknowledgments or other instruments as ROCHE may reasonably
request in connection with such assignment.
Enzyme/PCR Research Products 23 v.2061097
<PAGE>
10. NEGATION OF WARRANTIES AND INDEMNITY
10.1 Nothing in this Agreement shall be construed as:
a) a warranty or representation by ROCHE as to the validity or
scope of any patent included within POLYMERASE PATENT
RIGHTS, AMPLIFICATION PATENT RIGHTS, SEQUENCING PATENT
RIGHTS or RT AND RT-PCR PATENT RIGHTS;
b) a warranty or representation that the practice of
POLYMERASE PATENT RIGHTS, AMPLIFICATION PATENT RIGHTS,
SEQUENCING PATENT RIGHTS or RT AND RT-PCR PATENT RIGHTS is
or will be free from infringement of patents of third
parties;
c) an obligation to bring or prosecute actions or suits
against third parties for infringement, provided, however,
that this clause shall not alter INVITROGEN's rights and
ROCHE's obligations under Section 7.1;
d) except as expressly set forth herein, conferring the right
to use in advertising, publicity or otherwise any
trademark, trade name, or names, or any contraction,
abbreviation, simulation or adaptation thereof, of ROCHE or
P-E;
e) conferring by implication, estoppel or otherwise any
licenses, immunities or rights under any patents or patent
applications of ROCHE other than those specified in
POLYMERASE PATENT RIGHTS, AMPLIFICATION PATENT RIGHTS,
SEQUENCING PATENT RIGHTS or RT AND RT-PCR PATENT RIGHTS,
regardless of whether such other patents or patent
applications are dominant or subordinate to those in
POLYMERASE PATENT RIGHTS, AMPLIFICATION PATENT RIGHTS,
SEQUENCING PATENT RIGHTS or RT AND RT-PCR PATENT RIGHTS, or
under any thermal cycler or other instrument patent, or to
perform PCR in the thermal cycler that is not an AUTHORIZED
THERMAL CYCLER, or to make or sell any thermal cycler or
other instrument for the automated performance of the PCR
PROCESS;
f) an obligation to furnish any know-how not provided in
POLYMERASE PATENT RIGHTS, AMPLIFICATION PATENT RIGHTS,
SEQUENCING PATENT RIGHTS and RT AND RT-PCR PATENT RIGHTS;
or
g) creating any agency, partnership, joint venture or similar
relationship between ROCHE and/or P-E on the one hand, and
INVITROGEN on the other hand.
10.2 ROCHE MAKES NO EXPRESS OR IMPLIED WARRANTIES OF MERCHANTABILITY OR
FITNESS FOR A PARTICULAR PURPOSE.
10.3 Notwithstanding the foregoing, ROCHE warrants and represents that
it has the right to grant the licenses provided in Sections 2 and
5.
10.4 The provisions of Section 10.1 and 10.2 regarding warranties and
representations by ROCHE shall be specifically included in any
sublicense granted by INVITROGEN.
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<PAGE>
11. INDEMNITY
INVITROGEN shall assume full responsibility for its use of POLYMERASE
PATENT RIGHTS and for its sale of ROCHE PATENTED ENZYMES and
INVITROGEN ENZYMES and shall defend, indemnify and hold ROCHE and P-E
and their respective officers, directors, agents, employees and
stockholders, harmless from and against all liability, demands,
damages, expenses (including attorneys' and expert witness fees and
expenses) and losses for death, personal injury, illness or property
damage, or any other injury or damage arising out of the use by
INVITROGEN of the POLYMERASE PATENT RIGHTS or the preparation, use or
sale of LICENSED PRODUCTS, including but not limited to, use or
reliance upon such LICENSED PRODUCTS by customers of INVITROGEN.
12. *
13. GENERAL
13.1 This Agreement constitutes the entire agreement between INVITROGEN and
ROCHE as to the subject matter hereof, and all prior negotiations,
representations, agreements and understandings are merged into,
extinguished by and completely expressed by it. This Agreement may be
modified or amended only by a writing executed by authorized officers
of each of The Parties.
* "CONFIDENTIAL PORTION HAS BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION."
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<PAGE>
Any notice required or permitted to be given by this Agreement shall
be given by postpaid, first class, registered or certified mail, or by
courier, properly addressed to the other party or parties at the
respective address as shown below.
If to ROCHE: F. Hoffmann-La Roche Ltd
Grenzacherstrasse 124
4070 Basel
Switzerland
Attn: Corporate Law Department
with a copy to: Roche Molecular Systems, Inc.
1145 Atlantic Avenue, Suite 100
Alameda, California 94501
U.S.A.
Attn: Licensing Manager
If to INVITROGEN: Invitrogen Corporation
1600 Faraday Avenue
Carlsbad, California 92008
U.S.A.
Attn: Law Department
Either party may change its address by providing notice to the other
party. Unless otherwise specified herein, any notice given in
accordance with the foregoing shall be deemed given within four (4)
full business days after the day of mailing, or one full day after the
date of delivery to the courier, as the case will be.
13.2 GOVERNING LAW
This Agreement and its effect are subject to and shall be construed
and enforced in accordance with the laws of Switzerland
13.3 ARBITRATION
The Parties agree that all disputes arising from or in connection with
this Agreement, including disputes on its conclusion, binding effect,
amendment and termination, the exclusive jurisdiction and venue for
any such dispute or controversy shall be resolved, to the exclusion of
the ordinary courts, by an Arbitral Tribunal in accordance with the
International Arbitration Rules of the Zurich Chamber of Commerce.
13.4 Nothing in this Agreement shall be construed so as to require the
commission of any act contrary to law, and wherever there is any
conflict between any provision of this Agreement or concerning the
legal right of the parties to enter into this Agreement and any
statute, law, ordinance or treaty, the latter shall prevail, but in
such event the affected provisions of the Agreement shall be curtailed
and limited only to the extent necessary to bring it within the
applicable legal requirements.
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<PAGE>
13.5 If any provision of this Agreement is held to be unenforceable for any
reason, it shall be adjusted rather than voided, if possible, in order to
achieve the intent of the parties to the extent possible. In any event,
all other provisions of this Agreement shall be deemed valid and
enforceable to the full extent possible.
IN WITNESS WHEREOF, The Parties hereto have set their hands and seals and
duly executed this Agreement on the date(s) indicated below.
Basel, F. HOFFMANN-LA ROCHE LTD
By: /s/ [ILLEGIBLE]
--------------------------------
Title: PCR Licensing Manager Signatory
----------------------------
Date: September 19, 1998
------------------------------
Branchburg, ROCHE MOLECULAR SYSTEMS, INC.
Apprv'd As To Form By: /s/ Kathy Ordonez
LAW DEPT. ---------------------------------------
Kathy Ordonez
By: [ILLEGIBLE]
---- Title: President
Date: July 27, 1998
-------------------------------------
INVITROGEN CORPORATION
By: /s/ Joseph M. Fernandez
---------------------------------------
Joseph M. Fernandez
Title: Vice President, Business Development
Date: 9/1/98
-------------------------------------
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<PAGE>
S C H E D U L E 1
POLYMERASE PATENT RIGHTS(1)
4,889,818
5,079,352
5,352,600
USSN 07/873,897
USSN 08/384,490
----------------
(1) And those Ex-US patents and patent applications which claim priority from
the above-referenced US Patents and patent applications and access to which is
necessary for INVITROGEN to manufacture, use and sell the ROCHE PATENTED ENZYMES
specifically listed in Schedule 2 hereto. For the convenience of INVITROGEN,
Roche shall provide to INVITROGEN, from time to time as appropriate, an up-dated
list of its worldwide patent portfolio directed to POLYMERASE PATENT RIGHTS.
Enzyme/PCR Research Products 28 v.2061097
<PAGE>
S C H E D U L E 2
ROCHE PATENTED ENZYMES(1) licensed herein:
a) native Taq DNA Polymerase, full length, unmutated
b) recombinant Taq DNA Polymerase, full length, unmutated
c) Tth DNA Polymerase, full length, unmutated (native or recombinant)
----------------
(1) To the extent that any of the enzymes listed above may be covered by third
party patent rights, no rights under such third party patent are hereby
granted or implied.
Enzyme/PCR Research Products 29 v.2061097
<PAGE>
A P P E N D I X A
APPLICATIONS FIELDS
FORENSICS AND HUMAN IDENTITY APPLICATIONS
1. "Forensic and Human Identity Applications" shall mean the forensic
analysis of human genetic material for use in, or in preparation for,
legal proceedings, but shall exclude parentage determination except in
cases of sexual assault investigation. This field specifically excludes
tissue typing.
2. *
ENVIRONMENTAL TESTING APPLICATIONS
1. "Environmental Testing Applications" shall mean testing and monitoring
environmental samples, including, without limitation, for the purpose of
detecting the presence or absence or amount of any organism or
microorganism (including, without limitation, viruses and bacteria),
whether living, dead or extinct, or their remains.
2. *
AGRICULTURAL PLANT APPLICATIONS
1. "Agricultural Plant Applications" shall mean diagnostic applications in
plants, including, without limitation, the diagnosis of a disease or
condition, the diagnosis of susceptibility or resistance to a disease or
condition, or a choice of treatment of a disease or condition, the
determination of genetic traits for breeding purposes, or the
identification of a particular plant species.
2. *
ANIMAL IDENTITY TESTING AND POSITIVE TRAIT BREEDING APPLICATIONS
1. "Animal Identity Testing Applications" shall mean identity testing for
animals (other than humans) whether living, dead or extinct, or their
remains, including, without limitation, parentage determination.
"Positive Trait Breeding Applications" shall mean the determination of
genetic traits other than disease-related traits for breeding purposes.
2. *
* "CONFIDENTIAL PORTION HAS BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION."
Enzyme/PCR Research Products 30 v.2061097
<PAGE>
FOOD TESTING APPLICATIONS
1. "Food Testing Applications" shall mean the detection and/or analysis of
microorganisms in food or food/samples for quality assurance and quality
control purposes.
2. *
* "CONFIDENTIAL PORTION HAS BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION."
Enzyme/PCR Research Products 31 v.2061097
<PAGE>
APPENDIX B
ASSAY TO DETERMINE UNITS OF ENZYME
1. Taq DNA polymerase
Taq DNA polymerase manufactured by INVITROGEN ("INVITROGEN-Taq") shall be
assayed under the following conditions, in parallel with an assay of
Roche Molecular Systems' AmpliTaq-Registered Trademark- DNA polymerase
(P-E catalogue numbers N-801-0060, N-801-1012). The activity of
INVITROGEN-Taq and AmpliTaq thus measured by INVITROGEN shall be
normalized to the concentration stated by RMS for the AmpliTaq.
Unit Definition: One unit of enzyme is defined as the amount that
will incorporate 10nmoles of dNTPs into acid
insoluble material per 30 minutes at 74 deg. C under
the analysis conditions below.
Analysis conditions: 25mM TAPS (tris-(hydroxymethyl)-methyl-amino-
propane-sulfonic acid, sodium salt) pH 9.3 (at
25 deg. C); 50mM KCl; 2mM MgCl(2);
1mM Beta-mercaptoethanol; 200muM each dATP, dGTP,
dTTP; 100muM [infinity - (32)P]-dCTP (0.05 to
0.1 Ci/mmole); activated salmon sperm DNA, mixed in
a final volume of 50mul and incubated at 74 deg. C
for 10 minutes. The salmon sperm DNA is activated by
a modification of the methods in reference 1.
The assay mixture (without enzyme) is prepared fresh daily and 45mul
aliquots (0 deg. C) are mixed with 5mul of Taq DNA polymerase diluted in
25mM Tris-HCl pH 8, 50mM KCl, 100mug/ml autoclaved gelatin, 1mM
Beta-mercaptoethanol, 0.5% (w/v) NP40 and 0.5% (w/v) Tween20.
Reactions are initiated with addition of enzyme and placed at 74 deg. C.
Reactions are quenched after 10 minutes with the addition of 10mul of
60mM EDTA and placed at 0 deg. C. Aliquots (50mul) are diluted with 1ml
of 2mM EDTA containing 50mug/ml sheared salmon sperm DNA, and precipitated
by the addition of 1 ml 20% (w/v) trichloroacetic acid and 2% (w/v)
sodium pyrophosphate, and incubated at 0 deg. C for 15 min. Precipitated
DNA is collected on GF/C filter discs (2.4 cm) and washed extensively
with 5% trichloroacetic acid and 2% sodium pyrophosphate (7 x 5 ml), then
95% ethanol (5ml), dried and counted.
------------------------
(1) Richardson, C.C. 1966. DNA Polymerase from Escherichi coli. in PROCEDURES
IN NUCLEIC ACID RESEARCH eds. Cantoni G.L. and Davies, D.R. Harper &
Row, New York. p. 264.
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<PAGE>
Activity concentration is determined from replicate assays (at least 3)
of replicate parallel, serial dilutions (at least 3) that yield 20-90
pMoles dCMP incorporation in the assay.
Activated salmon sperm DNA is used at a concentration that provides
linear incorporation values with 20-100 mU of enzyme. This DNA
concentration usually represents 12.5-20mug/assay.
II. INVITROGEN ENZYMES AND ROCHE PATENTED ENZYMES OTHER THAN TAQ DNA
POLYMERASE
INVITROGEN ENZYMES shall be assayed in reference to AmpliTaq DNA
polymerase (or another enzyme manufactured by ROCHE which is more
comparable to the particular INVITROGEN ENZYME) in a manner similar to
that described above. The analysis conditions shall be adapted to
reflect the optimal activity conditions for each such INVITROGEN ENZYME.
Further, the effectiveness of such enzyme in producing amplified DNA in
the PCR PROCESS shall be determined in comparison with AmpliTaq DNA
polymerase under the optimal conditions for each enzyme. This
determination shall be performed as follows:
TEMPLATE: Bacteriophage Lambda DNA
TARGET: The 500 basepair fragment of bacteriophage lambda DNA extending
from nucleotides 7131 to 7630 will be the target for amplification.
Note: The template and primers are available in the GeneAmp-Registered
Trademark- Lambda Control Reagents (Part No. N808-0008) from Perkin-Elmer.
PRIMERS:
5'-GATGAGTTCGTGTCCGTACAACTGG-3' (complement of - strand: Nucleotides
7131-7155)
5'-GGTTATCGAAATCAGCCACAGCGCC-3' (complement of + strand: Nucleotides
7606-7630)
CONDITIONS:
200muM each dATP, dCTP, dGTP, dTTP, 1ng/100mul. template, 1muM each primer.
For AmpliTaq DNA polymerase other components are: 10mM Tris-HCl pH8.3,
1.5mM MgCl(2) and 50mM KCl.
For INVITROGEN Enzyme, buffer pH and concentration, and MgCl(2) and KCl
concentrations should be optimized for the INVITROGEN enzyme.
Enzyme/PCR Research Products 33 v.2061097
<PAGE>
The PCR should be carried out for 25 cycles.
From the comparative yield of specific 500 basepair fragment, a "PCR
Effectiveness Ratio" will be derived to be used in determining the
ROYALTY UNIT as specified in Section 1.16. The Parties agree that
calculation of such a ratio is complex and the data supporting the
determination of the ratio must be reviewed and approved by ROCHE on a
case by case basis.
III. For purposes of calculating royalties owed on products, the concentration
of enzyme (units per volume) reported must be within * of the actual
activity measured by the above assays. The volume of enzyme reported
to be in a product must be within +/- * of the actual measurable volume.
* "CONFIDENTIAL PORTION HAS BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION."
Enzyme/PCR Research Products 34 v.2061097
<PAGE>
APPENDIX C
NOTICES TO PURCHASER
1. LICENSE STATEMENT FOR USE ON ROCHE PATENTED ENZYMES AND INVITROGEN ENZYMES
DESIGNED AND SOLD FOR USE IN AMPLIFICATION PATENT RIGHTS AND/OR SEQUENCING
PATENT RIGHTS.
NOTICE TO PURCHASER: LIMITED LICENSE
A license under U.S. Patents 4,683,202, 4,683,195, 4,965,188, and 5,075,216
or their foreign counterparts, owned by Roche Molecular Systems, Inc. and
F. Hoffmann-La Rouche Ltd ("Roche"), has an up-front fee component and a
running-royalty component. The purchase price of this product includes
limited, nontransferable rights under the running-royalty component to use
only this amount of the product to practice the Polymerase Chain Reaction
("PCR") and related processes described in said patents solely for the
research and development activities of the purchaser when this product is
used in conjunction with a thermal cycler whose use is covered by the
up-front fee component. Rights to the up-front fee component must be
obtained by the end user in order to have a complete license to use this
product in the PCR process. These rights under the up-front fee component
may be purchased from Perkin-Elmer or obtained by purchasing an Authorized
Thermal Cycler. No right to perform or offer commercial services of any
kind using PCR, including without limitation reporting the results of
purchaser's activities for a fee or other commercial consideration, is
hereby granted by implication or estoppel. Further information on
purchasing licenses to practice the PCR Process may be obtained by
contacting the Director of Licensing at The Perkin-Elmer Corporation, 850
Lincoln Centre Drive, Foster City, California 94404 or at Roche Molecular
Systems, Inc., 1145 Atlantic Avenue, Alameda, California 94501.
2. LICENSED RESEARCH PRODUCTS DESIGNED AND SOLD FOR USE IN AMPLIFICATION
PATENT RIGHTS BUT NOT SUITABLE FOR USE IN SEQUENCING PATENT RIGHTS
NOTICE TO PURCHASER: LIMITED LICENSE
A license under U.S. Patents 4,683,202, 4,683,195 and 4,965,188 or their
foreign counterparts, owned by Roche Molecular Systems, Inc. and F.
Hoffmann-La Roche Ltd ("Roche"), has an up-front fee component and a
running-royalty component. The purchase price of this product includes
limited, nontransferable rights under the running-royalty component to use
only this amount of the product to practice the Polymerase Chain Reaction
("PCR") and related processes described in said patents solely for the
research and development activities of the purchaser when this product is
used in conjunction with a thermal cycler whose use is covered by the
up-front fee component. Rights to the up-front fee component must be
obtained by the end user in order to have a complete license. These rights
under the up-front fee component may be purchased from Perkin-Elmer or
obtained by purchasing an Authorized Thermal Cycler. No right to perform
or offer commercial services of any kind using PCR, including without
limitation reporting the results of
Enzyme/PCR Research Products 35 v.2061097
<PAGE>
purchaser's activities for a fee or other commercial consideration, is
hereby granted by implication or estoppel. Further information on
purchasing licenses to practice the PCR Process may be obtained by
contacting the Director of Licensing at The Perkin-Elmer Corporation, 850
Lincoln Centre Drive, Foster City, California 94404 or at Roche Molecular
Systems, Inc., 1145 Atlantic Avenue, Alameda, California 94501.
3. LICENSED RESEARCH PRODUCTS DESIGNED AND SOLD FOR USE IN SEQUENCING RIGHTS
NOTICE TO PURCHASER: LIMITED LICENSE
The purchase price of this product includes a limited, nontransferable
license under U.S. Patent 5,075,216 or its foreign counterparts, owned by
Roche Molecular Systems, Inc. and F. Hoffmann-La Roche Ltd ("Roche"), to
use only this amount of the product for DNA Sequencing and related
processes described in said patent solely for the research and development
activities of the purchaser. No license under these patents to use the PCR
process is conveyed expressly or by implication to the purchaser by the
purchase of this product. A license to use the PCR Process for certain
research and development activities accompanies the purchase of certain
reagents from licensed suppliers such as INVITROGEN when used in
conjunction with an Authorized Thermal Cycler, or is available from The
Perkin-Elmer Corporation. Further information on purchasing licenses to
practice the PCR Process may be obtained by contacting the Director of
Licensing at The Perkin-Elmer Corporation, 850 Lincoln Centre Drive, Foster
City, California 94404 or at Roche Molecular Systems, Inc., 1145 Atlantic
Avenue, Alameda, California 94501.
4. FOR USE ON RESEARCH PRODUCTS WHICH ARE NOT LICENSED RESEARCH PRODUCTS BUT
WHICH ARE SUPPORTED FOR USE IN PCR AND/OR WITH LICENSED RESEARCH PRODUCTS
NOTICE TO PURCHASER
This product is optimized for use in the Polymerase Chain Reaction ("PCR")
covered by patents owned by Roche Molecular Systems, Inc. and F.
Hoffmann-La Roche Ltd ("Roche"). No license under these patents to use the
PCR Process is conveyed expressly or by implication to the purchaser by the
purchase of this product. A license to use the PCR Process for certain
research and development activities accompanies the purchase of certain
reagents from licensed suppliers such as INVITROGEN when used in
conjunction with an authorized thermal cycler, or is available from The
Perkin-Elmer Corporation. Further information on purchasing licenses to
practice the PCR Process may be obtained by contacting the Director of
Licensing at The Perkin-Elmer Corporation, 850 Lincoln Centre Drive, Foster
City, California 94404 or at Roche Molecular Systems, Inc., 1145 Atlantic
Avenue, Alameda, California 94501.
5. Similar notices for use on products for RT and RT-PCR and for Licensed
Application Products will be provided as appropriate.
Enzyme/PCR Research Products 36 v.2061097
<PAGE>
SUMMARY ROYALTY REPORT APPENDIX D
for the Period _______ to ________ US or x-US: ___________
Licensee: Invitrogen Corporation Field of Use: Enzyme/PCR Research Products
Effective Date: July 1, 1998 Royalty Rate: 15.5 cents/unit or 15% of Net Sales
------------------------------------------------------------------------------------------------------------------------------------
Units of Gross Invoice Discounts Number Royalty
Licensed Product Enzyme in Price of Allowed Net Sales of Product Determined on Royalty Due
Product Product (Explain) of Product Units Sold Enzyme or Net
Sales
------------------------------------------------------------------------------------------------------------------------------------
------------------------------------------------------------------------------------------------------------------------------------
------------------------------------------------------------------------------------------------------------------------------------
------------------------------------------------------------------------------------------------------------------------------------
------------------------------------------------------------------------------------------------------------------------------------
------------------------------------------------------------------------------------------------------------------------------------
------------------------------------------------------------------------------------------------------------------------------------
------------------------------------------------------------------------------------------------------------------------------------
Check here if there were no sales for this period _______ TOTAL ROYALTY EARNED
-----------------------------------------------------
*Please attach supporting or supplemental data to this sheet. APPLICABLE CREDIT
-----------------------------------------------------
ROYALTY PAYMENT DUE
------------------------------------------------------------------------------------------------------------------------------------
I hereby certify the information set forth above is correct and complete with respect to the amounts due under
the applicable license agreement.
By: Title: Date:
------------------------------ ---------------------- ---------
(authorized signature)
Name (PLEASE PRINT):
--------------------------------
Send to: Applied Biosystems Division, The Perkin-Elmer Corporation, 850 Lincoln
Centre Dr., Foster City, CA 94404
copy to: Roche Molecular Systems, Inc., 1145 Atlantic Avenue, Suite 100,
Alameda, CA 94501
Enzyme/PCR Research Products 37 v.2061097